Background High glucose (HG)-induced reactive oxygen species (ROS) overproduction impairs angiogenesis that is one pivotal factor of wound healing process. Angiogenesis impairment induces delayed wound healing, whereby it eventually leads to amputation in cases of poorly controlled diabetes with diabetic ulceration. Porcine placenta extract (PPE) is a natural waste product that comprises plenty of bioactive agents including growth factors and antioxidants. It was reported as an effective compound that prevents ROS generation. The goal of this study was to investigate the in vitro effect of PPE on HG-induced ROS-mediated angiogenesis impairment. Methods Primary endothelial cells (HUVECs) and endothelial cell line (EA.hy926) were treated with HG in the presence of PPE. The endothelial cells (ECs) viability, intracellular ROS generation, migration, and angiogenesis were determined by MTT assay, DCFDA reagent, wound healing assay, and tube formation assay, respectively. Additionally, the molecular mechanism of PPE on HG-induced angiogenesis impairment was investigated by Western blot. The angiogenic growth factor secretion was also investigated by the sandwich ELISA technique. Results HG in the presence of PPE significantly decreased intracellular ROS overproduction compared to HG alone. HG in the presence of PPE significantly increased ECs viability, migration, and angiogenesis compared to HG alone by showing recovery of PI3K/Akt/ERK1/2 activation. HG in the presence of PPE also decreased ECs apoptosis compared to HG alone by decreasing p53/Bax/cleaved caspase 9/cleaved caspase 3 levels and increasing Bcl 2 level. Conclusion PPE attenuated HG-induced intracellular ROS overproduction that improved ECs viability, proliferation, migration, and angiogenesis by showing recovery of PI3K/Akt/ERK1/2 activation and inhibition of ECs apoptosis. This study suggests PPE ameliorated HG-induced ROS-mediated angiogenesis impairment, whereby it potentially provides an alternative treatment for diabetic wounds.

Damage-associated molecular patterns (DAMPs) are well recognized as the molecular signature of immunogenic cell death (ICD). The efficacy of drug-induced ICD function may be impacted by the precise ratio between immunostimulatory and immunoinhibitory DAMPs. Tumor-derived DAMPs can activate tumor-expressed TLRs for the promotion of tumor cell motility, invasion, metastatic spread and resistance to chemotherapeutic treatment. Herein, drug-induced DAMPs’ expression and their role in tumor progression are utilized as one crucial point of evaluation regarding chemotherapeutic treatment efficacy in our study. Cisplatin and oxaliplatin, the conventional anticancer chemotherapy drugs, are emphasized as a cause of well-known DAMPs’ release from cholangiocarcinoma (CCA) cells (e.g., HSP family, S100, CRT and HMGB1), whereby they trigger Akt, ERK and Cyclin-D1 to promote tumor activities. These findings strengthen the evidence that DAMPs are not only involved in immunomodulation but also in tumor promotion. Therefore, DAMP molecules should be considered as either targets of cancer treatment or biomarkers to evaluate treatment efficacy and tumor recurrence.

Modern cancer immunotherapy techniques are aimed at enhancing the responses of the patients' immune systems to fight against the cancer. The main promising strategies include active vaccination of tumor antigens, passive vaccination with antibodies specific to cancer antigens, adoptive transfer of cancer-specific T cells and manipulation of the patient's immune response by inhibiting immune checkpoints. The application of immunogenic cell death (ICD) inducers has been proven to enhance the immunity of patients undergoing various types of immunotherapy. The dying, stressed or injured cells release or present molecules on the cell surface, which function as either adjuvants or danger signals for detection by the innate immune system. These molecules are now termed ‘damage-associated molecular patterns’. The term ‘ICD’ indicates a type of cell death that triggers an immune response against dead-cell antigens, particularly those derived from cancer cells, and it was initially proposed with regards to the effects of anticancer chemotherapy with conventional cytotoxic drugs. The aim of the present study was to review and discuss the role and mechanisms of ICD as a promising combined immunotherapy for gastrointestinal tumors.

Porcine placenta extract (PPE) is an effective pharmaceutical and cosmetic ingredient, despite its high bioavailability. Despite this, only a few studies on the extract's effect on human osteoblast cellular behavior have been conducted. This study used hFOB 1.19 cells to demonstrate the mechanism by which a novel potent osteogenic compound that was discovered by stimulating the growth, alkaline phosphatase secretion, mineralization, and osteogenesis markers of human osteoblast hFOB 1.19 cells resulted in significant increases in extracellular signal-regulated kinase (ERK)1/2, Akt, and c-Jun N-terminal kinase (JNK) phosphorylation. In addition, PPE was discovered to significantly increase in vitro bone formation that may provide the beneficial potential for osteoporosis prevention and treatment.